X-124334064-A-T

Variant names:

• chrX-124334064-A-T
• rs181190185
• NM_001355534.2:c.1147A>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001355534.2(TEX13D):​c.1147A>T​(p.Met383Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000484 in 933,998 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 132 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 7/10 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00033 (0 hom., 11 hem., cov: 21)
  • Exomes 𝑓: 0.00050 (0 hom. 121 hem.)
• Consequence: TEX13D NM_001355534.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.687
• Publications: 0 publications found

Genes affected

TEX13D (HGNC:52278): (TEX13 family member D) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

STAG2 (HGNC:11355): (STAG2 cohesin complex component) The protein encoded by this gene is a subunit of the cohesin complex, which regulates the separation of sister chromatids during cell division. Targeted inactivation of this gene results in chromatid cohesion defects and aneuploidy, suggesting that genetic disruption of cohesin is a cause of aneuploidy in human cancer. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

SH2D1A (HGNC:10820): (SH2 domain containing 1A) This gene encodes a protein that plays a major role in the bidirectional stimulation of T and B cells. This protein contains an SH2 domain and a short tail. It associates with the signaling lymphocyte-activation molecule, thereby acting as an inhibitor of this transmembrane protein by blocking the recruitment of the SH2-domain-containing signal-transduction molecule SHP-2 to its docking site. This protein can also bind to other related surface molecules that are expressed on activated T, B and NK cells, thereby modifying signal transduction pathways in these cells. Mutations in this gene cause lymphoproliferative syndrome X-linked type 1 or Duncan disease, a rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus, with symptoms including severe mononucleosis and malignant lymphoma. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

SH2D1A Gene-Disease associations (from GenCC):

• X-linked lymphoproliferative disease due to SH2D1A deficiency

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.062076658).
• BP6: Variant X-124334064-A-T is Benign according to our data. Variant chrX-124334064-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2661357.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd4 at 11 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001355534.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEX13D	NM_001355534.2	MANE Select	c.1147A>T	p.Met383Leu	missense	Exon 1 of 1	NP_001342463.1	A0A0J9YY54

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEX13D	ENST00000632372.3	TSL:6 MANE Select	c.1147A>T	p.Met383Leu	missense	Exon 1 of 1	ENSP00000488696.1	A0A0J9YY54
	STAG2	ENST00000469481.1	TSL:3	n.454-77758A>T		intron	N/A
	TEX13D	ENST00000635518.1	TSL:5	n.90-1288A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000330 AC: 36 AN: 109250 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000955

Gnomad ASJ AF: 0.00191

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000342

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000517

Gnomad OTH AF: 0.000678

GnomAD4 exome AF: 0.000504 AC: 416 AN: 824702 Hom.: 0 Cov.: 31 AF XY: 0.000475 AC XY: 121 AN XY: 254728

African (AFR) AF: 0.00 AC: 0 AN: 18029

American (AMR) AF: 0.000310 AC: 2 AN: 6461

Ashkenazi Jewish (ASJ) AF: 0.00197 AC: 21 AN: 10666

East Asian (EAS) AF: 0.0000489 AC: 1 AN: 20453

South Asian (SAS) AF: 0.0000705 AC: 1 AN: 14188

European-Finnish (FIN) AF: 0.000555 AC: 9 AN: 16204

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2023

European-Non Finnish (NFE) AF: 0.000531 AC: 373 AN: 702928

Other (OTH) AF: 0.000267 AC: 9 AN: 33750

GnomAD4 genome AF: 0.000329 AC: 36 AN: 109296 Hom.: 0 Cov.: 21 AF XY: 0.000345 AC XY: 11 AN XY: 31864

African (AFR) AF: 0.00 AC: 0 AN: 29926

American (AMR) AF: 0.0000954 AC: 1 AN: 10486

Ashkenazi Jewish (ASJ) AF: 0.00191 AC: 5 AN: 2617

East Asian (EAS) AF: 0.00 AC: 0 AN: 3380

South Asian (SAS) AF: 0.00 AC: 0 AN: 2503

European-Finnish (FIN) AF: 0.000342 AC: 2 AN: 5848

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 207

European-Non Finnish (NFE) AF: 0.000517 AC: 27 AN: 52175

Other (OTH) AF: 0.000670 AC: 1 AN: 1493

Alfa AF: 0.000918 Hom.: 5

Bravo AF: 0.000389

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.78
DANN	Benign	0.55
FATHMM_MKL	Benign	0.0043	N
LIST_S2	Benign	0.21	T
MetaRNN	Benign	0.062	T
PhyloP100		-0.69
Sift4G	Benign	0.44	T
Vest4		0.20
GERP RS		-1.4
Varity_R		0.31
gMVP		0.043

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs181190185; hg19: chrX-123467914;